1. Academic Validation
  2. Possible antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway inhibitor, in mice model of Schistosoma-induced liver fibrosis

Possible antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway inhibitor, in mice model of Schistosoma-induced liver fibrosis

  • Parasitol Int. 2017 Oct;66(5):545-554. doi: 10.1016/j.parint.2017.04.004.
Abeer A Elhenawy 1 Rehab H Ashour 2 Nairmen Nabih 3 Naglaa M Shalaby 3 Nirmeen Megahed 4
Affiliations

Affiliations

  • 1 Medical Parasitology Department, Faculty of Medicine, Mansoura University, Egypt. Electronic address: abirelhenawy@mans.edu.eg.
  • 2 Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Egypt.
  • 3 Medical Parasitology Department, Faculty of Medicine, Mansoura University, Egypt.
  • 4 Department of Pathology, Faculty of Medicine, Mansoura University, Egypt.
Abstract

Liver fibrosis is a pathological process complicating schistosomiasis. It is an active process of continuous extracellular matrix accumulation. In Egypt, schistosomiasis re-infection is a continuing problem especially in rural areas. In this study we examined the antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway inhibitor as a new molecular target for Schistosoma-induced liver fibrosis, in addition to exploring its effect as antischistosomal drug. The effect of GDC-0449 alone or combined with Praziquantel was tried experimentally in infected mice with Schistosoma mansoni. Fifty CD-1 Swiss female albino mice were used, forty mice were infected with Schistosoma mansoni cercariae. Animals were grouped into five groups; uninfected control, infected untreated, infected treated with Praziquantel (500mg/kg/day) for two days, infected treated with GDC-0449 (40mg/kg/day) for seven days, and infected treated with combined Praziquantel and GDC-0449. Parasitological and chemical parameters, hydroxyproline level and liver granuloma were assessed. Liver fibrosis was reduced significantly evidenced by reduced hydroxyproline levels [P<0.01 for combined (Praziquantel/GDC-0449) treatment groups, P<0.001 for GDC-0449-treated group]. Also, histopathological examination of liver tissues revealed that the mean diameter of granulomas was statistically reduced (P=0.001) with a reduction rate of 24.4% on treatment with GDC-0449. In GDC-0449/Praziquantel combined treatment group, number and mean diameter of the granulomas were reduced significantly P<0.001, and P=0.001 respectively. No antischistosomal effect was recorded for GDC-0449 in this study.

Keywords

GDC-0449; Hedgehog pathway; Liver fibrosis; Schistosomiasis; Vismodegib.

Figures
Products